A PROSPECTIVE RANDOMIZED TRIAL OF FK506 VERSUS CYCLOSPORINE AFTER HUMAN PULMONARY TRANSPLANTATION

We have conducted a unique prospective randomized study to compare the effect of FK506 and cyclosporine (CsA) as the principal immunosuppres sive agents after pulmonary transplantation. Between October 1991 and March 1993, 74 lung transplants (35 single lung transplants [SLT], 39 bilateral lung transplant [BLT]) were performed on 74 recipients who w ere randomly assigned to receive either FK or CsA. Thirty-eight recipi ents (19 SLT, 19 BLT) received FK and 36 recipients (16 SLT, 20 BLT) r eceived CsA. Recipients receiving FK or CsA were similar in age, gende r, preoperative New York Heart Association functional class, and under lying disease. Acute rejection (ACR) was assessed by clinical, radiogr aphic, and histologic criteria. ACR was treated with methylprednisolon e, 1 g i.v./day, for three days or rabbit antithymocyte globulin if st eroid-resistant. During the first 30 days after transplant, one patien t in the FK group died of cerebral edema, while two recipients treated with CsA died of bacterial pneumonia (1) and cardiac arrest (1) (P=NS ). Although one-year survival was similar between the groups, the numb er of recipients free from ACR in the FK group was significantly highe r as compared with the CsA group (P<0.05). Bacterial and viral pneumon ias were the major causes of late graft failure in both groups. The me an number of episodes of ACR/100 patient days was significantly fewer in the FK group (1.2) as compared with the Cs.A group (2.0) (P<0.05). While only one recipient (1/36=3%) in the group treated with CsA remai ned free from ACR within 120 days of transplantation, 13% (5/38) of th e group treated with FK remained free from ACR during this interval (P <0.05). The prevalence of bacterial infection in the CsA group was 1.5 episodes/100 patient days and 0.6 episodes/100 patient days in the FK group. The prevalence of cytomegaloviral and fungal infection was sim ilar in both groups. Although the presence of bacterial, fungal, and v iral infections was similar in the two groups, ACR occurred less frequ ently in the FK-treated group as compared with the CsA-treated group i n the early postoperative period (<90 days). Early graft survival at 3 0 days was similar in the two groups, but intermediate graft survival at 6 months was better in the FK group as compared with the CsA group.